Urinary Biomarkers Predict Weaning From Acute Dialysis Therapy

Acute kidney injury is associated with a higher risk of chronic kidney disease (CKD), end-stage renal disease, and long-term adverse cardiovascular effects. Critically ill patients with acute kidney injury (AKI) requiring renal replacement therapy (RRT) have a poor prognosis.

Several urinary biomarkers that can predict the development of AKI have been identified, including proximal renal tubular damage markers (e.g., liver-type fatty acid–binding protein [L-FABP], hemojuvelin [HJV], and kidney injury molecule 1 [KIM-1]), distal renal tubular damage markers (e.g., neutrophil gelatinase-associated lipocalin [NGAL] ), and inflammation markers (e.g., C-C motif chemokine ligand 14 [CCL14] and interleukin 18 [IL-18].

Nephrologists at the National Taiwan University Hospital (Taipei, Taiwan) and their colleagues prospectively recorded and analyzed clinical variables at several time points: (1) before starting renal replacement therapy (RRT), (2) at the time of weaning off RRT, and (3) 24 hours after stopping RRT. A total of 140 critically ill patients who received RRT at a multicenter referral hospital from August 2016 to January 2019 were enrolled.

At the time of stopping RRT, urine samples were collected and stored at −80 °C until analysis. The urine concentrations of novel AKI biomarkers were determined using enzyme-linked immunosorbent assay kits: renal L-FABP, (Sekisui Medical Co, Ltd, Tokyo, Japan); KIM-1, NGAL, CCL14 and IL-18, (R&D Systems, Minneapolis, MN, USA), HJV, (Cloud-Clone Corp, Katy, TX, USA).

The investigators reported that the 90-day mortality rate was 13.6% (19/140), and 47.9% (67/140) of the patients were successfully weaned from RRT. Cluster analysis showed that the following biomarkers were correlated with estimated glomerular filtration rate at the time of weaning off RRT: urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule 1, hemojuvelin, C-C motif chemokine ligand 14, interleukin 18, and liver-type fatty acid–binding protein (L-FABP). Among these, urinary L-FABP/creatinine (uL-FABP/Cr) at the time of weaning off RRT showed the best predictive performance for mortality (area under the receiver operating characteristic curve = 0.79).

The authors concluded that nearly half of the critically ill AKI-RRT patients in this study were successfully weaned from acute RRT. They demonstrated that uL-FABP/Cr level at the time of weaning from RRT independently predicted being dialysis free for more than 90 days and all-cause mortality. They also showed that a cutoff value of uL-FABP/Cr (log) level ≤ 2.2 μg/g Cr may be useful for clinical decision-making for AKI-RRT patients who attempt to wean off RRT. uL-FABP/Cr can be combined with SOFA score at the time of weaning off RRT to predict being dialysis free and 90-day mortality. The study was published in the November, 2022 issue of the journal Archives of Pathology & Laboratory Medicine.

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